Molecular Architecture and Control of Enterococcus faecalis biofilms: Implications for Anti-virulence Therapy.

Authors

Divya Goel, Sudhir Kumar

Published in

Infectious disorders drug targets. Nov 04, 2026. Epub Nov 04, 2026.

Abstract

Enterococcus faecalis is a major opportunistic pathogen found especially in healthcare settings and is responsible for persistent and recurrent infections. Its remarkable survival and virulence can be attributed to its capacity to form robust biofilms on host tissues and medical devices. Biofilm-associated growth confers enhanced antibiotic tolerance, protects against host immune responses, and facilitates long-term colonization. The molecular mechanisms underlying E. faecalis biofilm development, encompassing the sequential stages of surface attachment, microcolony formation, maturation, and dispersal, have been of particular interest for therapeutic interventions. Key surface-associated factors, including enterococcal surface protein (Esp), endocarditis- and biofilm-associated pili (Ebp), aggregation substance, and Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs), collectively mediate adhesion to biotic and abiotic surfaces and promote intercellular aggregation. The growth of the biofilm is mainly driven by enterococcal polysaccharide antigen (EPA) and extracellular DNA, both of which are critical for structural integrity and antimicrobial tolerance. Autolysis-dependent eDNA production, carried out by extracellular proteases, i.e., gelatinase (GelE) and serine protease (SprE), under the regulation of the Fsr quorum sensing (QS) system, is crucial for biofilm development in E. faecalis. Several global regulatory networks linked to stress adaptation, cell envelope homeostasis, and antimicrobial resistance could also affect biofilm physiology in E. faecalis. Several of these factors and regulatory pathways have been the target of emerging anti-biofilm strategies. These strategies might include small molecules, antimicrobial peptides, nanoparticles, and bacteriophages. Since biofilm development and sustainability are multifactorial processes, understanding their regulatory architecture will aid the development of effective therapeutic approaches against persistent enterococcal infections.

PMID:
43021760
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.

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